Ole Goertz

Host defense peptides in wound healing.

Host defense peptides are effector molecules of the innate immune system. They show broad antimicrobial action against gram-positive and -negative bacteria, and they likely play a key role in activating and mediating the innate as well as adaptive immune response in infection and inflammation. These features make them of high interest for wound healing research. Non-healing and infected wounds are a major problem in patient care and health care spending. Increasing infection rates, growing bacterial resistance to common antibiotics, and the lack of effective therapeutic options for the treatment of problematic wounds emphasize the need for new approaches in therapy and pathophysiologic understanding. This review focuses on the current knowledge of host defense peptides affecting wound healing and infection. We discuss the current data and highlight the potential future developments in this field of research.

Limb Salvage in Malignant Tumors

Limb-sparing resection and reconstruction has become the treatment of choice in extremity malignancies, as amputation does not provide better long-term survival rates or functional advantages. R0 resection, the removal of the tumor in sano, remains the prerequisite and most important oncologic parameter to avoid local recurrence. Successful treatment requires the combination of surgical eradication and the patients specific functional and aesthetic rehabilitation. Our clinical rationale resulting from more than 2000 cases will be demonstrated. The problematic aspects of different tumor entities and the locoregional clearance of lymphatic pathways will be discussed. Differential diagnosis and multimodality treatment in high-volume tumor centers is likely to achieve superior oncologic statistics. Long-term survivors after microsurgical reconstructions and possible secondary malignancies will be addressed.

Leiomyosarcoma of intravascular origin - a rare tumor entity: clinical pathological study of twelve cases

BackgroundLeiomysarcoma of intravascular origin is an exceedingly rare entity of malignant soft tissue tumors. They are most frequently encountered in the retroperitoneum arising from the inferior vena cava and are scarcely found to arise from vessels of the extremities. These tumors were analysed with particular reference to treatment outcome and prognosis. The aim of this article is to broaden the knowledge of the clinical course of this rare malignancy.MethodDuring 2000 and 2009 twelve patients were identified with an intravascular origin of a leiomyosarcoma. Details regarding the clinical course, follow-up and outcome were assessed with focus on patient survival, tumor relapse and metastases and treatment outcome. 3 year survival probability was calculated using Kaplan-Meier method.ResultsVascular leiomyosarcomas accounted for 0.7% of all malignant soft tissue tumors treated at our soft tissue sarcoma reference center. The mean follow up period was 38 months. Tumor relapse was encountered in six patients. 6 patients developed metastatic disease. The three year survival was 57%.ConclusionVascular leiomysarcoma is a rare but aggressive tumor entity with a high rate of local recurrence and metastasis.

Vergleichende In-vitro-Studie zur Zytotoxizität klinisch eingesetzter Antiseptika

ZusammenfassungHintergrundAntiseptika zur Behandlung chronischer und infizierter Wunden gehören zur Standardtherapie. Erkenntnisse über toxische Eigenschaften gegenüber dem Wund- und Hautgewebe sind jedoch kaum vorhanden. Diese Studie untersucht den Einfluss von Wundantiseptika auf die Vitalität und Proliferation humaner kutaner Zellen.Material und MethodenDie Antiseptika Lavasept (PHMB), Octenisept (Octenidin) und Betaisodona (PVP-Jod) wurden mittels MTT-Assay und BrDU-ELISA auf zytotoxische Effekte gegenüber der HaCaT-Zelllinie, primären humanen Keratinozyten und Fibroblasten untersucht.ErgebnisseLavasept besaß nur geringen Einfluss auf Vitalität und Zellproliferation. Betaisodona und Octenisept induzierten eine signifikante Reduktion der Zellvitalität (p<0,05) bis zu 0% überlebender Fibroblasten bei 7,5% (Betaisodona) bzw. 10% (Octenisept) sowie der Zellproliferation auf 0% bei Keratinozyten durch Konzentrationen von 7,5% (Betaisodona und Octenisept).SchlussfolgerungDie Studie zeigt, dass herkömmlich verwendete Wundantiseptika deutlich toxische Effekte besitzen. Sowohl antimikrobielle Potenz als auch toxische Eigenschaften der einzelnen Antiseptika müssen bei der Wundbehandlung berücksichtigt werden. Insgesamt zeigte die PHMB-Lösung (Lavasept) die geringste toxische Wirkung.AbstractPurposeLocal skin antiseptics are the standard of care for chronic and non-healing wounds. However, little is known about their potential toxic properties. This study investigates the impact of three commercially available and widely used antiseptics on vitality and proliferation of human cutaneous cells.Material and MethodsThree antiseptics, Lavasept (PHMB), Octenisept (octenidine) and Betaisodona (PVP-iodine) were tested for their cytotoxic effects towards HaCaT cells, primary human keratinocytes and fibroblasts using MTT assay and BrDU ELISA.ResultsLavasept showed only slight to moderate toxic effects on cellular vitality and proliferation. Ocentisept and Betaisodona induced severe reduction of cell vitality (p<0.05) to 0% surviving fibroblasts at 7.5% (Betaisodona) and 12.5% Octenisept, respectively. Furthermore, poliferative activity was reduced to 0% in keratinocytes at 7.5% concentration of Betaisodona and Ocentisept.ConclusionThis study shows that frequently used wound- and skin antiseptics show severe cytotoxic effects towards cutaneous cells. Furthermore, antimicrobial efficacy and toxic properties must be included in the clinical decision process for optimal therapy of chronic wounds. The PHMB solution Lavasept showed best results regarding toxicity in this study.PURPOSE Local skin antiseptics are the standard of care for chronic and non-healing wounds. However, little is known about their potential toxic properties. This study investigates the impact of three commercially available and widely used antiseptics on vitality and proliferation of human cutaneous cells. MATERIAL AND METHODS Three antiseptics, Lavasept (PHMB), Octenisept (octenidine) and Betaisodona (PVP-iodine) were tested for their cytotoxic effects towards HaCaT cells, primary human keratinocytes and fibroblasts using MTT assay and BrDU ELISA. RESULTS Lavasept showed only slight to moderate toxic effects on cellular vitality and proliferation. Ocentisept and Betaisodona induced severe reduction of cell vitality (p<0.05) to 0% surviving fibroblasts at 7.5% (Betaisodona) and 12.5% Octenisept, respectively. Furthermore, poliferative activity was reduced to 0% in keratinocytes at 7.5% concentration of Betaisodona and Ocentisept. CONCLUSION This study shows that frequently used wound- and skin antiseptics show severe cytotoxic effects towards cutaneous cells. Furthermore, antimicrobial efficacy and toxic properties must be included in the clinical decision process for optimal therapy of chronic wounds. The PHMB solution Lavasept showed best results regarding toxicity in this study.

The pedicled gastrocnemius muscle flap: a review of 218 cases.

Background: Data regarding donor-site morbidity, postoperative clinical course, and functional and aesthetic outcome after gastrocnemius muscle flaps are rare. Methods: Data regarding 218 consecutive patients treated with gastrocnemius muscle flaps were acquired from patients’ charts and from contact with patients, with special reference to treatment and clinical course. Eighty-two were interviewed with a standardized questionnaire, 40 were examined physically, and 34 underwent dynamometric muscle function tests. Results: The authors observed wound-healing difficulties in 7 percent, wound infections in 4 percent, and one flap loss; 4.5 percent of the lateral gastrocnemius patients suffered from postoperative palsy of the peroneal nerve. Eighty-seven percent were not significantly limited walking on even ground, but only 42 percent could run, and 40 percent complained about pain when walking more than 200 m. The average range-of-motion deficit in the ankle joint for flexion and extension was 11 percent and 10 percent, respectively. The maximal plantar flexion force in the ankle joint of the operated leg was 76.2 percent. Strength endurance was reduced approximately 24.4 percent in the operated leg compared with the nonaffected side. Conclusions: Gastrocnemius muscle transfer represents a safe and simple procedure in the treatment of lower leg defects and in limb preservation. The strength loss and functional impairment (and sensation disorders) are considerable but may not be exclusively attributable to the muscle transfer but rather the result of the preceding trauma, infection, or tumor resection. The donor-site morbidity is well tolerated by the majority of the patients.

Influence of anti-inflammatory and vasoactive drugs on microcirculation and angiogenesis after burn in mice

OBJECTIVE The treatment of burns remains a challenge. Besides the administration of physiological saline, local disinfection and symptomatic medications, no causal therapy is known to accelerate angiogenesis and wound healing. The aim of this study was to investigate the influences of dilatative and anti-inflammatory acting drugs on microcirculation, angiogenesis and leukocyte behavior, which had shown positive effects in former burn studies. METHODS The ears of male hairless mice (n=47) were inflicted with full thickness burns using a hot air jet. Then the affects of five intraperitoneal injections of either acetylsalicylic acid (ASA), isosorbide dinitrate, prostaglandin E1 (PGE1) or sodium chloride (each administered to one of four corresponding study groups), on microcirculation, leukocyte-endothelial interaction and angiogenesis were investigated over a 12 day period using intravital fluorescent microscopy. RESULTS Angiogenesis was slightly improved by PGE1 (0.3 vs. 1.3% non-perfused area in other groups on day 12, p=0.029). Additionally, blood flow increased and rolling leukocytes decreased compared to other groups. The ASA-group showed best functional vessel density and lowest leukocyte-adhesion. The often described posttraumatic expansion of tissue damage could not be observed in either group. CONCLUSION Prostaglandin E1 improved angiogenesis, increased the blood flow and reduced the number of rolling leukocytes. ASA had positive influences on functional vessel density, edema formation and the number of sticking leukocytes. However, it reduced the blood flow. Overall, out of all the drugs tested, prostaglandin seems to have the greatest positive impact on microcirculation and angiogenesis in burns.

Intravital Pathophysiologic Comparison of Frostbite and Burn Injury in a Murine Model

BACKGROUND The breakdown of skin microcirculation and the leukocyte-endothelium interaction are assumed to play key roles in the pathophysiology of burn and frostbite injuries. Available data on frostbite and burn injuries were collected using different experimental models and setups, which limits direct comparisons of these thermal traumata significantly. To determine pathophysiologic similarities and differences, two comparable in vivo frostbite and burn models were used to assess microcirculatory and angiogenetic changes in burn and frostbite injuries. MATERIALS AND METHODS Either deep partial thickness no-touch burns or frostbite injuries were inflicted to the ears of hairless mice (n = 40) by a hot or cold gas jet (117.0 ± 2.1°C for 1 s and -195.8 ± 2.7°C for 1.5 s, respectively) resulting in a necrotic, nonperfused area of about 1.56 ± 0.28 mm2. Intravital fluorescent microscopy was used in combination with fluorescent dyes in order to assess the microcirculation, angiogenesis, and leukocyte-activity over a 12-d period. RESULTS The angiogenesis occurred significantly faster after frostbite than after burn (16.4% ± 4.5% versus 30.6% ± 2.8% nonperfused area, compared with the baseline value on d 7 (P = 0.009)). The loss of functional vessel density was significantly more pronounced after frostbite (57.6% ± 2.2% versus 89.2% ± 4.9% (P < 0.001)). However, the area recovered faster. The edema formation, as a parameter for endothelial integrity, was significantly more pronounced and lasted longer after frostbite, compared with the burn injury, and reached its maximum level on d 7 after trauma (162.4% ± 4.2% versus 142.% ± 5.9%; P = 0.007). In contrast to the rolling leukocytes, which showed the same increase on d 1 and then a subsequent decrease in both groups, the number of adherent leukocytes after the burn was markedly higher on d 1 (480% versus 167%; P = 0.001) but decreased much faster. The number of adherent leukocytes after frostbite remained significantly higher than those of the burn group during the entire observation. CONCLUSION The comparison of analogous intravital burn and frostbite models indicates that despite the similarities, decisive microcirculatory differences in extension and recovery from these two types of thermal trauma exist.

Orthogonal polarization spectral imaging: a tool for assessing burn depths?

The estimation of burn depths is still a challenge, and even experienced surgeons often fail. In search of an objective method for differentiation between deep- and partial-thickness burns, we investigated the use of orthogonal polarization spectral (OPS) imaging to visualize the microcirculation in burn wounds.Twenty-seven burned patients were included in the study, 81 burn areas were investigated at day 1 and 4 post burn. The final therapy was compared with the therapy that would have been carried out as a consequence of the OPS imaging result. The patients were treated conservatively with dressings or surgically with necrectomy and split skin grafts.A comparison of the estimation of the burn depths of OPS imaging with the final therapy showed a correlation of 76.5%, about 5% less than the clinical assessment. It has proved a useful tool in particular for the prognosis as to whether the burn will heal spontaneously within 14 days or not.The presented OPS-Imaging device provides additional qualitative and quantitative information about the perfusion of the skin and therefore facilitates decisions about the follow on therapy. It is not an alternative to an experienced burn surgeon but provides important additional information.

A comparative in vitro study of cell toxicity of clinically used antiseptics

ZusammenfassungHintergrundAntiseptika zur Behandlung chronischer und infizierter Wunden gehören zur Standardtherapie. Erkenntnisse über toxische Eigenschaften gegenüber dem Wund- und Hautgewebe sind jedoch kaum vorhanden. Diese Studie untersucht den Einfluss von Wundantiseptika auf die Vitalität und Proliferation humaner kutaner Zellen.Material und MethodenDie Antiseptika Lavasept (PHMB), Octenisept (Octenidin) und Betaisodona (PVP-Jod) wurden mittels MTT-Assay und BrDU-ELISA auf zytotoxische Effekte gegenüber der HaCaT-Zelllinie, primären humanen Keratinozyten und Fibroblasten untersucht.ErgebnisseLavasept besaß nur geringen Einfluss auf Vitalität und Zellproliferation. Betaisodona und Octenisept induzierten eine signifikante Reduktion der Zellvitalität (p<0,05) bis zu 0% überlebender Fibroblasten bei 7,5% (Betaisodona) bzw. 10% (Octenisept) sowie der Zellproliferation auf 0% bei Keratinozyten durch Konzentrationen von 7,5% (Betaisodona und Octenisept).SchlussfolgerungDie Studie zeigt, dass herkömmlich verwendete Wundantiseptika deutlich toxische Effekte besitzen. Sowohl antimikrobielle Potenz als auch toxische Eigenschaften der einzelnen Antiseptika müssen bei der Wundbehandlung berücksichtigt werden. Insgesamt zeigte die PHMB-Lösung (Lavasept) die geringste toxische Wirkung.AbstractPurposeLocal skin antiseptics are the standard of care for chronic and non-healing wounds. However, little is known about their potential toxic properties. This study investigates the impact of three commercially available and widely used antiseptics on vitality and proliferation of human cutaneous cells.Material and MethodsThree antiseptics, Lavasept (PHMB), Octenisept (octenidine) and Betaisodona (PVP-iodine) were tested for their cytotoxic effects towards HaCaT cells, primary human keratinocytes and fibroblasts using MTT assay and BrDU ELISA.ResultsLavasept showed only slight to moderate toxic effects on cellular vitality and proliferation. Ocentisept and Betaisodona induced severe reduction of cell vitality (p<0.05) to 0% surviving fibroblasts at 7.5% (Betaisodona) and 12.5% Octenisept, respectively. Furthermore, poliferative activity was reduced to 0% in keratinocytes at 7.5% concentration of Betaisodona and Ocentisept.ConclusionThis study shows that frequently used wound- and skin antiseptics show severe cytotoxic effects towards cutaneous cells. Furthermore, antimicrobial efficacy and toxic properties must be included in the clinical decision process for optimal therapy of chronic wounds. The PHMB solution Lavasept showed best results regarding toxicity in this study.PURPOSE Local skin antiseptics are the standard of care for chronic and non-healing wounds. However, little is known about their potential toxic properties. This study investigates the impact of three commercially available and widely used antiseptics on vitality and proliferation of human cutaneous cells. MATERIAL AND METHODS Three antiseptics, Lavasept (PHMB), Octenisept (octenidine) and Betaisodona (PVP-iodine) were tested for their cytotoxic effects towards HaCaT cells, primary human keratinocytes and fibroblasts using MTT assay and BrDU ELISA. RESULTS Lavasept showed only slight to moderate toxic effects on cellular vitality and proliferation. Ocentisept and Betaisodona induced severe reduction of cell vitality (p<0.05) to 0% surviving fibroblasts at 7.5% (Betaisodona) and 12.5% Octenisept, respectively. Furthermore, poliferative activity was reduced to 0% in keratinocytes at 7.5% concentration of Betaisodona and Ocentisept. CONCLUSION This study shows that frequently used wound- and skin antiseptics show severe cytotoxic effects towards cutaneous cells. Furthermore, antimicrobial efficacy and toxic properties must be included in the clinical decision process for optimal therapy of chronic wounds. The PHMB solution Lavasept showed best results regarding toxicity in this study.

Antimicrobial activity of clinically used antiseptics and wound irrigating agents in combination with wound dressings.

Background: A primary strategy for preventing and treating wound infection in chronic wounds is the use of topical antiseptics and wound irrigating agents. However, their interaction with commonly used wound dressings has not yet been investigated. In this study, the authors analyzed the antimicrobial activity of antiseptics and wound irrigating agents used with commercially available wound dressings. Methods: Five clinically used antiseptics and wound irrigating agents (Prontosan, Lavasept, Braunol, Octenisept, and Betaisodona) were tested in the presence or absence of 42 wound dressings against Staphylococcus aureus. The determination of antibacterial activity was performed by disk diffusion assay. Results: Povidone-iodine–based products showed sufficient antimicrobial activity in 64 to 78 percent of the combinations assessed (p > 0.01). The octenidine derivate Octenisept showed sufficient antimicrobial activity in 54 percent of combinations. Polyhexamethylene biguanide derivatives demonstrated sufficient antimicrobial activity in 32 percent of the combinations. Conclusion: This study revealed that commonly used wound dressings dramatically reduce antibacterial activity of clinically used antiseptics and wound irrigating agents in vitro.